Abstract

OBJECTIVE: The goal of this study was to evaluate the predictive value and relative contribution of noninvasive presurgical functional imaging modalities based on the authors' institutional experience in pursuing seizure-free surgical outcomes in children with medically refractory epilepsy.METHODS: This was a retrospective, single-institution, observational cohort study of pediatric patients who underwent evaluation and surgical treatment for medically refractory partial epilepsy between December 2003 and June 2016. During this interval, 108 children with medically refractory partial epilepsy underwent evaluation for localization and resective epilepsy surgery. Different noninvasive functional imaging modalities, including ictal SPECT, FDG-PET, and magnetoencephalography-magnetic source imaging, were utilized to augment a standardized paradigm (electroencephalography/semiology, MRI, and neuropsychology findings) for localization. Outcomes were evaluated at a minimum of 2 years (mean 7.5 years) utilizing area under the receiver operating characteristic curve analysis. Localizing modalities and other clinical covariates were examined in relation to long-term surgical outcomes.RESULTS: There was variation in the contribution of each test, and no single presurgical workup modality could singularly and reliably predict a seizure-free outcome. However, concordance of presurgical modalities yielded a high predictive value. No difference in long-term outcomes between inconclusive (normal or diffusely abnormal) and abnormal focal MRI results were found. Long-term survival analyses revealed a statistically significant association between seizure freedom and patients with focal ictal EEG, early surgical intervention, and no history of generalized convulsions.CONCLUSIONS: Comprehensive preoperative evaluation utilizing multiple noninvasive functional imaging modalities is not redundant and can improve pediatric epilepsy surgical outcomes.

Abstract

PURPOSE: Describe treatment patterns in patients from the United States with new-onset epilepsy, comparing those with and without lesional epilepsy.METHODS: In this observational study we used Truven Health MarketScan databases derived from commercial health insurance, Medicare and Medicaid claims covering at least 5 years, commencing in 2008. We identified incident epilepsy cases based on International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating epilepsy or recurrent seizures, taking into account antiepileptic drug (AED) claims, consistent with International League Against Epilepsy Commission on Epidemiology recommendations. We identified patients with lesional epilepsy when associated diagnoses indicated central nervous system infection, neoplasm, traumatic brain injury, stroke, senile dementia and static encephalopathy. Lesional and nonlesional cohorts were matched 1:1 on baseline characteristics of age, sex and insurance type for group comparisons.RESULTS: In unmatched cohorts lesional epilepsy patients (N = 15,302) were more commonly older (mean age 48.7 years) compared with nonlesional epilepsy patients (N = 15,970; mean age 18.5 years). Among lesional patients <20 years of age, the leading putative etiology was static encephalopathy, while among ages ≥20 years and older, the leading putative etiology was stroke or cerebrovascular disease. In matched cohorts (7063 patients each), those with lesional epilepsy were significantly less likely to be untreated at 1 year versus those with nonlesional epilepsy (37.2% vs 56.1%). In children and adults among matched cohorts, levetiracetam was the most common AED prescribed for initial AED therapy for the lesional (39.5%) and nonlesional (32.1%) groups. Lesional epilepsy patients on monotherapy were only slightly less likely than nonlesional epilepsy patients to be on the same AED 1 year after treatment initiation (55.6% vs 59.7%).SIGNIFICANCE: Compared with patients with lesional epilepsy, a higher proportion of patients with nonlesional epilepsy remain untreated 1 year after diagnosis. There were differences in AED selection by epilepsy etiology; levetiracetam is the most commonly prescribed drug for both cohorts.

Abstract

We aimed to evaluate putative predictors of symptoms and signs at admission for nonconvulsive seizure and to examine the impact of nonconvulsive seizures on short-term outcomes.We retrospectively collected consecutive abusive head trauma patients (<36 months of age) from the trauma registry at Children's Healthcare of Atlanta between 2009 and 2014. Multiple logistic regression was performed to assess the putative predictors for the occurrence of nonconvulsive seizures including clinical seizures, altered mental status, respiratory difficulty, and cardiac arrest at admission, while controlling for age, sex, and injury severity. The Mann-Whitney U test and the Fisher exact test were used to compare the short-term outcomes between patients with and without nonconvulsive seizures.Two hundred seventy patients with abusive head trauma were identified (male = 55.6%). The median age was 4 months (interquartile range = 2-8 months). Among 70 patients who underwent continuous electroencephalography (EEG), 40 had nonconvulsive seizures (57%) and 21 developed nonconvulsive status epilepticus (30%). Altered mental status at admission was associated with the occurrence of nonconvulsive seizures (odds ratio = 6.8, 95% confidence interval = 1.2-38.2, P = .03). Comparing patients with no seizures, those with nonconvulsive seizures were more likely to stay longer at hospital (9 days vs 14 days, P = .04) and to need rehabilitation (50.0% vs 63.2%, P = .03).Nonconvulsive seizures and nonconvulsive status epilepticus was highly prevalent in young pediatric patients with abusive head trauma. Presenting with altered mental status at admission was found to predict the occurrence of nonconvulsive seizures. Nonconvulsive seizures had an unfavorable impact on short-term outcomes.

Abstract

The objective of this study was to determine patient characteristics and antiepileptic drug (AED) treatment patterns in patients with newly diagnosed epilepsy in a United States (US) population followed for ≥180 days.In this retrospective cohort study, Commercial, Supplemental Medicare, and Medicaid insurance claims from US-based Truven Health MarketScan® claims database were analyzed for incident epilepsy cases (index date: January 2010-June 2013; prior baseline of 2 years [1 year for ages 1 to <2 years; none for those <1 year]). Cases met epilepsy criteria consistent with the International League Against Epilepsy diagnostic guidelines, with continuous medical and pharmacy enrollment without an epilepsy or seizure diagnosis or AED prescription during baseline. Treatment was classified as monotherapy (one AED for ≥90 continuous days), polytherapy (at least two AEDs for ≥90 days), or untreated (no AED claims but other pharmacy or healthcare claims). Treatment pattern comparisons used matched cohorts across seizure types.Of 58,757 incident cases, 50,838 had a follow-up of ≥180 days. The median (range) follow-up duration was 529 (180-1096) days. Patient characteristics were similar across seizure types (matched focal vs. generalized epilepsy, N = 9949 each). At 6 and 12 months post-index, 46.8% and 52.2% of patients, respectively, had received AED treatment. Of 29,226 patients receiving treatment, 74.7% and 1.6% received monotherapy and polytherapy for ≥90 days, respectively, as first-line treatment; remaining patients received AED for <90 days and were excluded. The probability of remaining on initial treatment after 1 year was 61.0% for monotherapy and 36.5% for polytherapy. The most common first-line AEDs were levetiracetam (44.4%), phenytoin (6.5%), valproic acid (6.4%), lamotrigine (6.3%), oxcarbazepine (5.7%), topiramate (5.5%), and gabapentin (5.3%).Although the majority of treated patients received AED monotherapy consistent with guidelines, suboptimal rates of AED treatment and persistence of first-line treatment after initial epilepsy diagnosis suggest that efforts are needed to improve patient care.

Abstract

OBJECTIVE The objective of this study was to evaluate mesial temporal electroencephalographic (EEG) monitoring, using an intraventricular strip electrode (IVSE) along the ventricular surface of the hippocampus, in children with medically intractable epilepsy. METHODS The authors reviewed 10 consecutive cases in which subdural electrode placements and mesial temporal monitoring were recommended. The median age of the patients was 12.7 years (range 4.5-19.3 years). Both grids and IVSE were placed in all patients. The 4-contact IVSE was used in 5 cases, and the 6-contact IVSE in the other 5 cases. The median number of contacts, including IVSE contacts, was 122 (range 66-181). A total of 182 seizures were analyzed. RESULTS The IVSE localized seizure-onset zones in 8 patients. The seizure-onset zone was identified exclusively by IVSE in 3 patients and was simultaneous in IVSE and subdural electrodes in 5 patients. Among the 5 patients with simultaneous onset on both IVSE and subdural electrodes, 4 had basal temporal onset and one had orbitofrontal and lateral midtemporal onset. In the remaining 2 patients, the absence of IVSE seizure onset permitted sparing of mesial temporal structures. An Engel Class Ia outcome was achieved in 9 of 10 cases. No complication was associated with IVSE placement. CONCLUSIONS Intracranial monitoring using IVSE offers an alternative in terms of quality of EEG recording. IVSE was useful in children who already required open craniotomy for intracranial monitoring over an extensive network of hyper-excitability.

Abstract

Neurobehavioral comorbidities can be related to underlying etiology of epilepsy, epilepsy itself, and adverse effects of antiepileptic drugs. We examined the relationship between neurobehavioral comorbidities and putative risk factors for epilepsy in children with newly diagnosed epilepsy. We conducted a retrospective analysis of children aged ≤18years in 50 states and the District of Columbia, using the Truven Health MarketScan® commercial claims and encounters database from January 1, 2009 to December 31, 2013. The eligible study cohort was continuously enrolled throughout 2013 as well as enrolled for any days during a baseline period of at least the prior 2years. Newly diagnosed cases of epilepsy were defined by International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or recurrent seizures and evidence of prescribed antiepileptic drugs during 2013, when neither seizure codes nor seizure medication claims were recorded during baseline periods. Twelve neurobehavioral comorbidities and eleven putative risk factors for epilepsy were measured. More than 6 million children were analyzed (male, 51%; mean age, 8.8years). A total of 7654 children were identified as having newly diagnosed epilepsy (125 per 100,000, 99% CI=122-129). Neurobehavioral comorbidities were more prevalent in children with epilepsy than children without epilepsy (60%, 99% CI=58.1-61.0 vs. 23%, CI=23.1-23.2). Children with epilepsy were far more likely to have multiple comorbidities (36%, 99% CI=34.3-37.1) than those without epilepsy (8%, 99% CI=7.45-7.51, P<0.001). Preexisting putative risk factors for epilepsy were detected in 28% (99% CI=26.9-29.6) of children with epilepsy. After controlling for demographics, neurobehavioral comorbidities, family history of epilepsy, and other risk factors than primary interest, neonatal seizures had the strongest independent association with the development of epilepsy (OR=29.8, 99% CI=23.7-37.3, P<0.001). Compared with children with risk factors but no epilepsy, those with both epilepsy and risk factors were more likely to have intellectual disabilities (OR=13.4, 99% CI=11.9-15.0, P<0.001). The epilepsy and intellectual disabilities could share the common pathophysiology in the neuronal network.

Abstract

This study aims to determine prevalence and incidence of epilepsy in the US pediatric population. We analyzed commercial claims and Medicaid insurance claims data between 2008 and 2012. Over 8 million continuously enrolled lives aged 0 to 19 years were included. Our definition of a prevalent case of epilepsy was based on International Classification of Diseases-coded diagnoses of epilepsy or seizures and evidence of prescribed antiepileptic drugs. Incident cases were identified in subjects continuously enrolled for ≥2 years of which the first 2 years had no indication of epilepsy or seizures. The overall prevalence estimate for 2012 was 6.8 per 1,000 children. The overall incidence estimate for 2012 was 104 per 100,000 pediatric population. This study provides estimates of the prevalence and incidence of epilepsy in the US pediatric population, using large claims datasets from multiple US population sectors. The findings appear reasonably representative of the US-insured pediatric population.

Abstract

This study aims to assess recurrence risk in developmentally and neurologically normal children with a newly diagnosed unprovoked seizure. The medical record was retrospectively reviewed in 393 children who had a newly diagnosed, unprovoked seizure. A total of 152 children met inclusion criteria. The relationship between seizure recurrence and variables was examined. Seventy cases had recurrent seizures. Total 113 cases had follow-up data and 70 cases of these (63.7%) experienced recurrent seizures. EEG was abnormal in 65 (44.8%): focal epileptiform abnormality in 34 cases (23.4%) and generalized epileptiform abnormality in 23 cases (15.9%). Brain MRI revealed any structural abnormality in 14 of 86 cases (16.3%). Neither EEG abnormality nor brain MRI abnormality was statistically significantly associated with increased seizure recurrence in this cohort. Further study is required to confirm the EEG and brain MRI findings in otherwise normal children with a newly diagnosed unprovoked seizure.

Abstract

To investigate the relationship between EEG source localization and the number of scalp EEG recording channels.128 EEG channel recordings of 5 pediatric patients with medically intractable partial epilepsy were used to perform source localization of interictal spikes. The results were compared with surgical resection and intracranial recordings. Various electrode configurations were tested and a series of computer simulations based on a realistic head boundary element model were also performed in order to further validate the clinical findings.The improvement seen in source localization substantially decreases as the number of electrodes increases. This finding was evaluated using the surgical resection, intracranial recordings and computer simulation. It was also shown in the simulation that increasing the electrode numbers could remedy the localization error of deep sources. A plateauing effect was seen in deep and superficial sources with further increasing the electrode number.The source localization is improved when electrode numbers increase, but the absolute improvement in accuracy decreases with increasing electrode number.Increasing the electrode number helps decrease localization error and thus can more ably assist the physician to better plan for surgical procedures.

Abstract

To investigate the validity of magnetic source imaging (MSI) to localize seizure-onset zone using 3D analysis of pre-operative MSI source imaging coregistered to post-resection MRI following neocortical epilepsy surgery.Twenty-two children who had MSI and epilepsy surgery were studied (median age=11 years, 1 year 2 months-22 years). Only seven (31.8%) had localized lesions on pre-operative conventional brain MRIs. Sixteen (72.7%) underwent intracranial EEG monitoring. Mean post-operative follow-up was 4.7 years (1 year 3 months-8 years 2 months). Fifteen patients (68%) were seizure-free. MEG spike dipole sources were superimposed onto post-operative MRIs. The number and proportion of spike dipoles within resection volume were calculated and compared between seizure free and non-free groups.Both number of dipole clusters and proportion of dipoles in resection volume were not associated with seizure-free outcome (p>0.05). In seven cases with MRI lesions, six of these with a ≥70% dipoles within the resection margin were seizure-free, while one with the proportion <70% was not seizure-free. Further, among the 15 cases with non-localized or normal MRI, five with both the proportion <70% and multiple dipoles clusters were post-operatively seizure free.Number and density of clustered spike dipole sources within the surgical resection volume is not associated with postoperative seizure-free outcome. MSI successfully localized the perilesional epileptogenic zone in cases with localized MRI lesions, but not in cases with normal MRI in this study. Even if MEG localizes spikes to a single focal region, confirmation of epilepsy localization with intracranial EEG is still recommended in cases with non-lesional MRI.

Abstract

This study aimed to investigate the extent of microstructural changes in the major white matter fibers and to evaluate whether diffusion tensor imaging (DTI) adds any lateralizing information in children with medically intractable neocortical epilepsy secondary to focal cortical dysplasia. Patient group included twenty-three consecutively enrolled patients with medically intractable focal neocortical epilepsy and focal cortical dysplasia histopathologically confirmed. Thirteen patients (56.5%) had no visible lesion on the conventional magnetic resonance imaging (MRI). Fractional anisotropy (FA) was measured for regions of interest (ROIs) in each major white matter fiber. FA in patients was compared with eighteen age-matched healthy controls. Patient group had lower FA values at corpus callosum, bilateral inferior frontooccipital fasciculus (IFO), bilateral inferior longitudinal fasciculus (ILF) and left superior longitudinal fasciculus (SLF) compared to controls (p<0.05). In the left-side surgery group, the left SLF FA value was lower than controls, while in the right-side surgery group, the right SLF FA values were lower than controls (p<0.05). In the patient group as a whole, ipsilateral SLF FA was significantly lower than the contralateral SLF (p<0.05). Widespread decrease in FA values in the patients compared with the controls suggests that the pathologic changes extend diffusely to most major white matter tracts. In the patient group, the ipsilateral SLF to the seizure focus had greater change compared to the contralateral SLF. These data suggest that the detection of DTI abnormality has an added value to lateralization.

Abstract

Depth electrodes provide a better sampling of sulci and regions of cortex that lie tangential to the plane of subdural electrodes. The aim of this study was to evaluate the utility of supplemental depth electrodes in the surgical treatment of pediatric patients with neocortical epilepsy.Cases involving 12 consecutive pediatric patients (mean age [SD] 10.9 ± 4.4 years) were reviewed. Focal resective surgery (in 9 cases) or functional hemispherectomy (in 3 cases) was performed after intracranial monitoring. The mean total number of electrodes was 118 ± 29; the mean numbers of grid, strip, and depth electrodes were 95 ± 27, 10 ± 6, and 13 ± 5, respectively The most common pathological condition was focal cortical dysplasia.In 4 cases, depth electrodes demonstrated the ictal onset zone in an area not easily accessible by grids or strips (in the basal temporal region in 3 cases and the upper opercular region in 1 case). In 3 of these 4 cases, the ictal onset zone was defined exclusively by the depth electrodes. In each of these 3 cases, the surface electrodes (on grids or strips) demonstrated early propagation but not ictal onset. In 9 cases, the depth electrodes also demonstrated the early propagation zone. The information about the ictal onset zone and the early propagation zone helped to provide additional information that affected the extent (in 7 cases) or depth (in 3 cases) of the resection. The proportion of the electrodes involved in resection relative to the total number of implanted electrodes was low (mean ± SD, 0.26 ± 0.09). Nine patients (75.0%) became seizure free (Engel class IA outcome) after surgery (mean duration of follow-up 25.7 ± 4.29 months). There were no surgical complications related to intracranial electroencephalography monitoring.Most patients (75.0%) became seizure free after extensive monitoring and more limited resection of seizure-onset regions. Supplemental depth electrodes contribute to improved outcome by providing information about the ictal onset zone that is not accessible by grid or strip electrodes in some cases. The supplemental depth electrodes conferred an extra dimension of depth to the analysis, which allowed for successful outcome with more limited resection.

Abstract

We describe the case of a 10-year-old girl who developed behavioral changes consistent with Klüver-Bucy Syndrome following Listeria meningoencephalitis at 2½ years of age. MRI at age 4 revealed evidence of diffuse brain atrophy with predominant temporal lobe involvement. Electroencephalograpy at 9½ years of age showed abnormal electrical discharges from the left temporal area. Follow-up MRI with volumetric analysis of the mesial temporal structures at 9 years of age demonstrated decreased hippocampal volume bilaterally. Consistent with the morphological abnormalities, serial neuropsychological evaluations demonstrated expressive and receptive language impairment and an amnestic syndrome that significantly decreased her ability to make new declarative memories and maintain adequate academic progress.

Abstract

Methohexital has replaced amobarbital during Wada testing at many centers. The objective of our study was to compare the use of methohexital and amobarbital during Wada testing regarding language and memory lateralization quotients as well as speech arrest times.A chart review of 582 consecutive patients undergoing 1041 Wada-procedures was performed (left=60, right=63, bilateral=459). Language lateralization was calculated based on duration of speech arrest using a laterality index, defined as (L-R)/(L+R). Memory lateralization was expressed as percentage of retained objects and laterality quotient.Language and memory lateralization revealed a similar distribution with amobarbital and methohexital. Speech arrest after left and right-sided injection was significantly longer in the amobarbital group as compared to the methohexital group. Language lateralization did not differ in the two groups. Percentage of retained memory items was higher in the methohexital group and there were fewer presented test items in the methohexital group.Language and memory testing during the Wada test can successfully be performed with methohexital instead of amobarbital. The shorter half-life of methohexital allows repeated injections and shorter interhemispheric testing intervals, but also shortens the testing window.

Abstract

Imaging changes in patients with focal epilepsy are not only seen in areas where seizures arise but often also in remote locations. The mechanism for such changes is unknown. We aimed to investigate whether patients with temporal lobe epilepsy (TLE) have microstructural changes involving the posterior portion of the corpus callosum (CC), where it links the temporal lobes, using presurgical diffusion tensor imaging (DTI) sequences. Ten patients with medically intractable TLE (two mesial TLE, eight neocortical TLE) who had seizure-free surgical outcomes were compared with 10 healthy controls. The regions of interest were outlined at each Witelson region (WR). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and three principal diffusivity values (lambda1, lambda2, lambda3) were determined in each WR. We performed tractography originating at each WR. In the TLE patients, the FA values were lower at the splenium of the corpus callosum (WR 7) compared to controls (p<0.05). Analysis of Eigen values in that location revealed that lambda1 values were decreased while lambda2 and lambda3 values were increased (p<0.05). Tractography revealed the connection between both temporal lobes via WR 7. In conclusion, decreased FA values with decreased lambda1 and increased lambda2 and lambda3 at the splenium of CC suggest that the pathologic changes, Wallerian degeneration, extend to the corpus callosum in TLE patients. Seizure-induced damage may cause secondary white matter degeneration along the tapetum and through the splenium of the corpus callosum, a potential pathway of spread in temporal lobe seizures.

Abstract

Intracranial monitoring using electroencephalography (IC-EEG) continues to play a critical role in the assessment of patients with medically intractable localization-related epilepsy. There has been minimal change in grid or electrode design in the last 15-20 years, and the surgical approaches for implantation are unchanged. Intracranial monitoring using EEG allows detailed definition of the region of ictal onset and defines the epileptogenic zone, particularly with regard to adjacent potentially eloquent tissue. Recent developments of IC-EEG include the coregistration of functional imaging data such as magnetoencephalography to the frameless navigation systems. Despite significant inherent limitations that are often overlooked, IC-EEG remains the gold standard for localization of the epileptogenic cortex. Intracranial electrodes take a variety of different forms and may be placed either in the subdural (subdural strips and grids, depth electrodes) or extradural spaces (sphenoidal, peg, and epidural electrodes). Each form has its own advantages and shortcomings but extensive subdural implantation of electrodes is most common and is most comprehensively discussed. The indications for intracranial electrodes are reviewed.